Cholinergic metabolism and synapse formation by a rat nerve cell line.

Abstract

The PC12 clone of a rat pheochromocytoma is able to synthesize acetylcholine. The amount of acetylcholine synthesized, and the specific activity of choline O-acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), varies as a function of the culture growth curve and is dependent on cell density. The specific activity of choline acetyltransferase is increased by nerve growth factor, growth-conditioned medium from a variety of cell types, and adenosine 3':5'-monophosphate. Finally, the PC12 cell line is able to form cholinergic synapses with a clonal cell line of skeletal muscle origin.

Selective Regulation of Agrin mRNA Induction and Alternative Splicing in PC12 Cells by Ras-dependent Actions of Nerve Growth Factor

“…Our results indicate that agrin gene expression is also a synapse-related target of neurotrophin action. Our observation that differentiated PC12 cells contain mRNA encoding an agrin isoform with high AChR aggregating activity may also be relevant to the reported ability of PC12 cells to form functional synapses when co-cultured with L6 skeletal muscle cells (50). Given that growth factors present in muscle, including members of the neurotrophin family, influence motor neurons (51), it will be important in future studies to determine if the patterns of agrin gene expression in motor neurons and other primary neuronal populations are the consequence of the growth factor receptors they express and the soluble growth factors to which they are exposed.…”

Convergent Effects of Lithium and Valproate on the Expression of Proteins Associated with Large Dense Core Vesicles in NGF-differentiated PC12 Cells

“…These effects were detected in NGF-differentiated PC12 cells, but not in undifferentiated cells. Since NGFdifferentiated PC12 cells acquire a more neuron-like phenotype in the differentiated state (Tischler and Greene, 1975;Dichter et al, 1977;Schubert et al, 1977), these data imply that there may be environmental factors that dictate the sensitivity of specific cells or cell populations to these drugs. Moreover, lithium and valproate augmented the expression of VMAT1 which is largely confined to LDCV, and we detected no effect of these drugs on the expression of proteins (VAChT or SY), which are predominantly associated with SSV (Liu et al, 1994;Liu and Edwards, 1997).…”

Nerve Growth Factor Up-regulates the Transcriptional Activity of CBP through Activation of the p42/p44MAPK Cascade

“…PC12 cells respond to NGF by acquiring a reversible sympathetic neuronal like morphology that is preceded by a cycle of cell division. Several signal transduction pathways have been implicated in mediating the NGF-signaling including PKAs, PKC, and MAPKS (3)(4)(5). To investigate involvement of the PKA pathway in NGF-induced up-regulation of CBP activity, similar experiments were carried out in a PKA-deficient PC12 cell line, in which mutant regulatory subunits of PKA were stably expressed (25).…”

“…NGF exerts its growth-and survival-promoting effects on neurons through activation of its receptor TrkA and subsequent initiation of intracellular signaling cascades that ultimately influence the expression of various genes (2). Several signal transduction pathways have been implicated in mediating the intracellular components of the NGF signal including protein kinase C (3), the cAMP-dependent protein kinases (PKAs) (4), and the ras-dependent mitogen-activated protein kinases (MAPKs) (5). One transcription factor that is a key target of the NGF-stimulated signaling pathway is the cyclic AMP response element binding (CREB) protein (6,7).…”